This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Chronic immune activation and progression to AIDS are observed after SIV infection in macaques but not in other primate species. Methods: To better understand this dichotomy, we compared phenotypic markers, levels of immune activation and degree of depletion of subsets of CD4 T cells such as Th17 and Treg cells during acute pathogenic SIV infection in pigtailed macaques (PTMs) to nonpathogenic infection in African green monkeys, by flow-cytometry and microarrays. Results and Discussion: SIVagm-infected PTMs, but not SIVagm-infected AGMs, rapidily developed systemic immune activation, marked and selective depletion of IL-17-secreting TH17 cells and loss of the balance between Th17 and T regulatory cells in blood, LNs and mucosal tissues. The loss of Th17 cells was found to be predictive of systemic and sustained T cell activation. Collectively, these data indicate that loss of the Th17 to Treg balance is related to SIV disease progression.